Weiwei Chen

Optic Neuropathy Induced by Experimentally Reduced Cerebrospinal Fluid Pressure in Monkeys

PURPOSE To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical coherence tomographic and photographic images of the optic nerve head and RNFL were taken of all monkeys. RESULTS Two out of four monkeys in the study group showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%, reduction in neuroretinal rim area and volume, and increase in cup-to-disc area ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The fourth monkey in the study group did not develop morphologic changes during follow-up, nor did any monkey in the control group. CONCLUSIONS Experimental and chronic reduction in CSF in monkeys was associated with the development of an optic neuropathy in some monkeys.

Structural brain alterations in primary open angle glaucoma: a 3T MRI study

Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma.

Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study

To determine the interdependence of intracranial pressure (ICP) and intraocular pressure (IOP) and how it affects optic nerve pressures, eight normal dogs were examined using pressure-sensing probes implanted into the left ventricle, lumbar cistern, optic nerve subarachnoid space in the left eye, and anterior chamber in the left eye. This allowed ICP, lumbar cistern pressure (LCP), optic nerve subarachnoid space pressure (ONSP) and IOP to be simultaneously recorded. After establishing baseline pressure levels, pressure changes that resulted from lowering ICP (via shunting cerebrospinal fluid (CSF) from the ventricle) were recorded. At baseline, all examined pressures were different (ICP0.001). As ICP was lowered during CSF shunting, IOP also dropped in a parallel time course so that the trans-lamina cribrosa gradient (TLPG) remained stable (ICP-IOP dependent zone). However, once ICP fell below a critical breakpoint, ICP and IOP became uncoupled and TLPG changed as ICP declined (ICP-IOP independent zone). The optic nerve pressure gradient (ONPG) and trans-optic nerve pressure gradient (TOPG) increased linearly as ICP decreased through both the ICP-IOP dependent and independent zones. We conclude that ICP and IOP are coupled in a specific pressure range, but when ICP drops below a critical point, IOP and ICP become uncoupled and TLPG increases. When ICP drops, a rise in the ONPG and TOPG creates more pressure and reduces CSF flow around the optic nerve. This change may play a role in the development and progression of various ophthalmic and neurological diseases, including glaucoma.

The effect of increased intra-abdominal pressure on orbital subarachnoid space width and intraocular pressure

In accordance with the trans-lamina cribrosa pressure difference theory, decreasing the trans-lamina cribrosa pressure difference can relieve glaucomatous optic neuropathy. Increased intracranial pressure can also reduce optic nerve damage in glaucoma patients, and a safe, effective and noninvasive way to achieve this is by increasing the intra-abdominal pressure. The purpose of this study was to observe the changes in orbital subarachnoid space width and intraocular pressure at elevated intra-abdominal pressure. An inflatable abdominal belt was tied to each of 15 healthy volunteers, aged 22–30 years (12 females and 3 males), at the navel level, without applying pressure to the abdomen, before they laid in the magnetic resonance imaging machine. The baseline orbital subarachnoid space width around the optic nerve was measured by magnetic resonance imaging at 1, 3, 9, and 15 mm behind the globe. The abdominal belt was inflated to increase the pressure to 40 mmHg (1 mmHg = 0.133 kPa), then the orbital subarachnoid space width was measured every 10 minutes for 2 hours. After removal of the pressure, the measurement was repeated 10 and 20 minutes later. In a separate trial, the intraocular pressure was measured for all the subjects at the same time points, before, during and after elevated intra-abdominal pressure. Results showed that the baseline mean orbital subarachnoid space width was 0.88 ± 0.1 mm (range: 0.77–1.05 mm), 0.77 ± 0.11 mm (range: 0.60–0.94 mm), 0.70 ± 0.08 mm (range: 0.62–0.80 mm), and 0.68 ± 0.08 mm (range: 0.57–0.77 mm) at 1, 3, 9, and 15 mm behind the globe, respectively. During the elevated intra-abdominal pressure, the orbital subarachnoid space width increased from the baseline and dilation of the optic nerve sheath was significant at 1, 3 and 9 mm behind the globe. After decompression of the abdominal pressure, the orbital subarachnoid space width normalized and returned to the baseline value. There was no significant difference in the intraocular pressure before, during and after the intra-abdominal pressure elevation. These results verified that the increased intra-abdominal pressure widens the orbital subarachnoid space in this acute trial, but does not alter the intraocular pressure, indicating that intraocular pressure is not affected by rapid increased intra-abdominal pressure. This study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-ONRC-14004947).

Reduced Functional and Anatomic Interhemispheric Homotopic Connectivity in Primary Open-Angle Glaucoma: A Combined Resting State-fMRI and DTI Study

Purpose To investigate if abnormal interhemispheric homotopic functional connectivity were accompanied by corresponding anatomic connectivity changes in primary open-angle glaucoma (POAG) patients, and to relate connectivity changes with retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were performed in 16 POAG patients and 19 healthy controls. Indices of interhemispheric homotopic functional connectivity and the underlying anatomic connectivity changes were derived with voxel-base whole-brain voxel-mirrored homotopic connectivity (VMHC) analyses and VMHC-guided probabilistic tractography. Pearson correlation analyses were used to explore the correlations between interhemispheric homotopic functional connectivity changes and anatomic connectivity alterations, and RNFL and GCC thickness. Results Reduced VMHC values between bilateral homotopic cortical areas located in Brodmann area (BA)17, BA18, and BA19. Decreased anatomic connectivity connecting bilateral visual cortical areas inside BA17 and BA18 were observed in POAG patients. Furthermore, positive correlations between average RNFL thickness and reduced VMHC values of BA17 (r = 0.572, P = 0.021)/BA18 (r = 0.600, P = 0.014)/BA19 (r = 0.550, P = 0.027) are found using Pearson correlation analyses. Conclusions Combinations of interhemispheric homotopic functional connectivity and anatomic connectivity changes may help to elucidate the mechanism of interhemispheric synchronization injury in POAG patients. Reduced VMHC values positively correlate with glaucomatous changes of RNFL thickness, which strengthens the hypothesis that POAG affects the visual cortex using a novel functional MRI characteristic.

Noninvasive evaluation of cerebrospinal fluid pressure in ocular hypertension: a preliminary study

To compare the orbital cerebral spinal fluid pressure (CSFP) and trans‐lamina cribrosa pressure difference (TLCPD) determined noninvasively in ocular hypertensive (OH) subjects and controls.

Non-invasive Evaluation of Cerebrospinal Fluid Pressure in Ocular Hypertension: The Beijing Intracranial and Intraocular Pressure Study

Objective: To compare the orbital CSFP and trans-lamina cribrosa pressure difference (TLCPD) determined noninvasively in Ocular Hypertension (OH) and controls, and study its association with the estimated risk of conversion to glaucoma. Design: Cross-sectional observational study. Participants: 19 subjects with OH recruited from the Tongren Eye Center and 23 controls enrolled in the Beijing Intracranial and Intraocular Pressure Study between June 2010 to December 2013. Methods: Magnetic resonance imaging was used to measure orbital subarachnoid space width (OSASW) at 3, 9 and 15 mm posterior to the globe. The CSFP (mmHg) was estimated from a published formula as 17.54 × MRI derived OSASW at 15 mm behind the globe +0.47 × body mass index +0.13 × mean arterial blood pressure -21.52. Estimated TLCPD was calculated as IOP- CSFP. The values of CSFP and TLCPD were compared between OH and controls. The estimated risk of progression to glaucoma in OH was calculated and its correlation with CSFP determined. Main outcome measures: Orbital subarachnoid space width; MRI derived CSFP value; TLCPD value. Association of risk of progression with CSFP. Results: The orbital subarachnoid space width was significantly wider (P=0.01) in the OH group than in the control groups at all three measurement locations. The MRI derived CSFP value in OH (14.9 ± 2.9 mmHg) was significantly higher than in the normal group (12.0 ± 2.8 mmHg; P<0.01). The estimated TLCPD value in OH (9.0 ± 4.2 mmHg) was significantly higher than in controls (3.6 ± 3.0 mmHg; P<0.01). The estimated risk of conversion to glaucoma in OH (15.2 ± 8.7%) was negatively correlated with the MRI derived CSFP value (r=-0.51, r2=-0.26, P<0.01). Conclusions: The wider OSASW and higher estimated CSFP in OH subjects suggest a higher orbital CSFP. Despite a higher orbital CSFP that could be protective, the higher TLCPD in OH may play a significant role in the risk of developing glaucoma.

Author Response: Optic Neuropathy Secondary to Spontaneous Intracranial Hypotension (SIH) as Related to Experimental Primate Model

We thank Groth and colleagues for their interest in our study. The clinical situation presented by Groth and colleagues illustrated an optic disk–related optic neuropathy that may be partially similar to the optic neuropathy observed in the monkeys with experimentally low cerebrospinal fluid (CSF) pressure. It may be another example showing the potential importance of the CSF pressure as one determinant of the translaminar cribrosa pressure difference.